Prospective study of thyroid function in the first year of life in infants with Down syndrome.

Current American Academy of Pediatrics (AAP) Guidelines recommend monitoring thyroid function in infants with Down syndrome (DS) at birth, 6 and 12 months, and annually thereafter. This study aimed to determine whether these guidelines are optimal for early diagnosis and treatment of (subclinical) hypothyroidism. Enrolled infants with DS less than age 7 months, born at ≥ 30 weeks gestation to monitor thyroid function test (TFT). A filter paper (FP) blood sample was analyzed for TSH and total T4 at ages 2 and 4 weeks and monthly thereafter until 12 months. Subjects with abnormal FP sample and confirmatory serum TFT for hypothyroidism promptly started treatment. Subjects with thyroid dysfunction identified had thyroid antibodies measured at diagnosis and 12 months. Descriptive statistics determined average time to diagnosis of abnormal TFT. Sixteen (30%) of 54 subjects were diagnosed with a thyroid disorder, the majority with subclinical hypothyroidism (SH) and 1 with hyperthyroidism. Diagnosis occurred in 6 (11%), 9 (17%), and 12 (22.2%) infants in the first 30, 60, and 90 days of life (DOL), respectively. Eight infants had an abnormal NBS and half were diagnosed with a thyroid disorder by DOL 8 and the remainder prior to 4 months. Among subjects with a normal NBS, four were diagnosed at a mean of 104 days and three at a mean of 101 days prior to the 6-month and 12-month routine screens, respectively.  Conclusion: Based on current AAP guidelines, thyroid disorder diagnosis would have been delayed in nearly 20% of the subjects. An additional TFT screen at 1 and 3 months can lead to earlier diagnosis and treatment. What is Known: • Current American Academy of Pediatrics (AAP) Guidelines recommend thyroid function tests (TFT) in infants with Down syndrome (DS) at birth and 6 and 12 months. • Peer- reviewed retrospective studies report an increased incidence of hypothyroidism in infants with DS undetected by the newborn screen (NBS) and prior to 6 months. What is New: • This prospective study monitored TFT in infants with DS at age 2 weeks and monthly throughout the first year of life. • The findings in this study support additional TFT screens at 1 and 3 months in infants with DS.

MRI T2/STIR epaxial muscle hyperintensity in some dogs with intervertebral disc extrusion corresponds to histologic patterns of muscle degeneration and inflammation.

Magnetic resonance imaging hyperintensity on T2-weighted turbo SE and STIR sequences of the paraspinal musculature in canine patients being imaged for thoracolumbar intervertebral disc extrusion is frequently observed but poorly understood in veterinary medicine. The objective of this prospective analytical study was to describe the histopathology of muscle hyperintensity in dogs with thoracolumbar intervertebral disc extrusions and to determine if a relationship exists between the presence of this hyperintensity and various patient factors. Twenty privately owned dogs who underwent surgical decompression of intervertebral disc extrusions diagnosed on MRI were enrolled (10 normal "control or nonaffected cases" without MRI paraspinal musculature hyperintensity and 10 "affected cases" with hyperintensity). Surgical biopsies of the epaxial musculature at the region of hyperintensity (affecteds) and at the site of the disc herniation (controls) were submitted for histopathology. The degree of myofiber degeneration and necrosis was scored using an ordinal scoring system: absent (0), minimal (10), mild (20), moderate (30), marked/severe (40), and massive (50). Associations between hyperintensity presence and patient age, weight, body condition, neurologic status, acuteness of onset, number of disc herniation sites, degree of spinal cord compression, and volume of herniated material were investigated. Nonaffected patients were significantly older (median age = 9.4 years) than affected patients (median age = 3.5 years), but no other significant associations were found. Acute myofiber degeneration/necrosis and intramuscular inflammation were observed in half of affected patients. Therefore, T2/STIR muscle hyperintensity in some patients with intervertebral disc extrusion may represent muscle degeneration and inflammation.

Evaluation of Three Human Cervical Fusion Implants for Use in the Canine Cervical Vertebral Column.

OBJECTIVE: To assess technical feasibility and mechanical properties of 3 locking plate designs (Zero-P, Zero-P VA, and Uniplate 2) for use in the canine cervical spine. STUDY DESIGN: Prospective ex vivo study. ANIMALS: Cadaver cervical spines from skeletally mature large breed dogs (n = 18). METHODS: Specimens were screened using radiography and allocated into balanced groups based on bone density. Stiffness of intact C4-C5 vertebral motion units was measured in extension, flexion, and lateral bending using nondestructive 4-point bend testing. Uniplate 2 was then implanted at C4-C5 and mechanical testing was repeated. Mechanical test data were compared against those from 6 spines implanted with monocortical screws, an allograft ring spacer, and PMMA. RESULTS: The Zero-P and Zero-P VA systems could not be surgically implanted due to anatomical constraints in the vertebral column sizes of the canine cervical spines used in this study. Fixation with Uniplate 2 or with screws/PMMA significantly increased stiffness of the C4-C5 vertebral motion units compared to unaltered specimens (P < .001) in extension. Stiffness of the titanium screw/PMMA fixation was significantly greater than the Uniplate 2 construct in extension. Flexion and lateral bending could not be evaluated in 3 of 6 specimens in the Uniplate 2 group due to failure at the bone/implant interface during extension testing. CONCLUSION: Fixation with Uniplate 2 was biomechanically inferior to screws/PMMA. Particularly concerning was the incidence of vertebral fracture after several testing cycles. Based on our results, Zero-P, Zero-P VA, and Uniplate 2 cannot be recommended for use in dogs requiring cervical fusion.

Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB).

Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.

Probabilistic risk assessment of sustainable fish consumption at sediment sites.

A probabilistic risk assessment (PRA) using a range of sustainable usual fish consumption rates (SUFCRs) was performed to evaluate the potential health risks from consuming resident fish at two contaminated sediment sites. The analysis focused on the Portland Harbor Superfund Site, a large river in Oregon, and Koppers Pond, a small pond in New York. At both sites, the sediment cleanup remedy is driven by PCBs in resident fish. The PRA fit probability distributions to inputs used to develop a distribution of SUFCR, the long-term fish consumption rate sustainably supported by a fishery, and other exposure parameters to calculate the range and likelihood of cancer risks and noncancer hazards for adult anglers. At the 95th percentile, which is often considered a reasonable maximum exposure (RME), the SUFCRs calculated using site-specific inputs are six- to ten-fold lower than the point estimate fish consumption rates used in the deterministic baseline human health risk assessment conducted for each site. The combination of sustainable fish consumption rates and probabilistic methods results in a range of risks and thereby provides more information than the more commonly used deterministic approach. For over 99% of the resident fish-consuming population, the potential cancer risks and noncancer hazards calculated in the PRA are below the deterministic estimates for the RME adult consumer at each site. The combination of PRA with the estimation of SUFCRs is a novel application of these techniques at contaminated sediment sites that provides critical information for risk management decision-making. Integr Environ Assess Manag 2023;19:830-843. © 2022 AECOM Technical Services, Inc and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Inorganic Arsenic Concentration in Fish Governed by Trophic Level and Size, not Water Concentration: Implications for Human Health Water Quality Criteria.

In 2019, the Idaho Department of Environmental Quality implemented a paired surface water and fish tissue data collection program to derive a state-specific bioaccumulation factor (BAF) for inorganic arsenic (iAs) as part of the development of new human health water quality criteria (HHWQC). No statistically significant relationship was found between total arsenic (tAs) or iAs in surface water and fish tissue. Fish body weight was the only parameter with a statistically significant effect on iAs concentration in fish tissue. The ratio of iAs to tAs in fish tissue declined significantly with both increasing trophic level and increasing body weight. The decrease in iAs concentration in fish tissue with increasing size and trophic level as well as the decrease in the proportion of tAs that is iAs with increasing trophic level are likely the result of metabolic transformation of iAs to organic As by organisms in each level of the aquatic food web. Although the linear regression-based BAF using the Idaho paired fish and water data best predicted observed iAs fish tissue concentrations compared to several alternative BAFs, it was not statistically significant (p < 0.05) and was a poor predictor (R2 = 0.01) of iAs concentrations in fish tissue. These results illustrate that iAs, and possibly other metals, in the natural environment do not conform with commonly used bioaccumulation models and the paradigm used by the US Environmental Protection Agency for determining HHWQC. These results indicate that modifications to the paradigm are necessary, such as a fish tissue criterion as Idaho has proposed, to assure that public health is protected. Environ Toxicol Chem 2023;42:1542-1552. © 2023 SETAC.

Ambient water quality criteria derived using probabilistic risk assessment.

National recommendations for numeric human health ambient water quality criteria (AWQC) for toxic substances are derived by the US Environmental Protection Agency (USEPA) using a deterministic approach that combines point estimates for exposure, toxicity, and acceptable risk. In accordance with the Clean Water Act, states, territories, and authorized tribes must either adopt these recommendations or modify and replace them with criteria using an alternative, scientifically defensible method. Recent reports have criticized the deterministic approach, stating that it suffers from compounded conservatism by selecting upper percentiles or maximum values for multiple inputs and that it cannot directly determine what portion of the population a given criterion protects. As an alternative, probabilistic risk assessment (PRA) has been promoted as a more transparent and robust method for deriving AWQC. Probabilistic risk assessment offers several advantages over the deterministic approach. For example, PRA uses entire data distributions rather than upper-percentile point estimates to specify exposures, thereby reducing compounded conservatism. Additionally, because it links acceptable risk targets with specific segments of the exposed population, PRA-based AWQC demonstrably protects multiple subsets of the population. To date, no study has quantitatively compared deterministic and PRA approaches and resulting AWQC using national inputs consistent with USEPA guidance. This study introduces a PRA method for deriving AWQC and presents case studies to compare probabilistically derived AWQC with USEPA's 2015 recommendations. The methods and results of this work will help federal and state regulators, water quality managers, and stakeholders better understand available approaches to deriving AWQC and provide context to assumption- and method-specific differences between criteria. Integr Environ Assess Manag 2023;19:501-512. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Cefepime extended infusion versus intermittent infusion: Clinical and cost evaluation.

Background: Extended infusion cefepime (1 gram every 6 hours administered over 3 hours) achieves pharmacodynamic efficacy against bacteria with a MIC of ≤8 mg/L in Monte Carlo simulations. This regimen has not been evaluated in clinical practice. Objective: Compare clinical and economic outcomes for cefepime by intermittent infusion and by extended infusion in the acute-care setting. Design: Single-center, retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Hospitalized adults who received cefepime between August 2016 and July 2018 with a diagnosis of sepsis or pneumonia. Methods: Clinical and economic outcomes were compared for patients who received empiric cefepime via intermittent infusion (30-minute infusion of 2 g every 8 hours) or extended infusion (3-hour infusion of 1 g every 6 hours). Clinical outcomes analyses were carried out using appropriate statistical methods. Results: Overall, 111 patients received intermittent infusion and 93 patients received extended infusion. Approximately half of the included patients had a positive culture for a bacterial pathogen (intermittent infusion 45.9% vs extended infusion 47.3%). Median hospital length of stay (intermittent infusion 6 days vs extended infusion 6 days; P = .67) and 90-day readmission rates (intermittent infusion 61.3% vs extended infusion 67.7%; P = .34) did not differ between the groups. Mortality was infrequent in both groups (intermittent infusion 2.9% vs extended infusion 1.5%; P = .45). Cefepime cost per patient was lower with cefepime by extended infusion: average total daily cost $86.06 for intermittent infusion versus $43.39 for extended infusion. Conclusions: Cefepime via extended infusion (4 grams/day) did not differ in clinical outcomes compared to intermittent infusion (6 grams/day) but reduced drug expenditure. Prospective, multicenter, high-quality studies should be conducted to evaluate a mortality difference between these regimens.

Birds and bats reduce insect biomass and leaf damage in tropical forest restoration sites.

Both birds and bats are important insect predators in tropical systems. However, the relative influence of birds and bats on insect populations and their indirect effects on leaf damage have not previously been investigated in tropical forest restoration sites. Leaf damage by herbivorous insects can negatively affect the growth and survival of tropical plants and thus can influence the success of tropical forest restoration efforts. We used an exclosure experiment to examine the top-down effects of birds and bats on insects and leaf damage in a large-scale forest restoration experiment. Given the potential influence of tree planting design on bird and bat abundances, we also investigated planting design effects on bird and bat insectivory and leaf damage. The experiment included two planting treatment plots: islands, where trees were planted in patches, and plantations, where trees were planted in rows to create continuous cover. In both types of plots, insect biomass was highest on tree branches where both birds and bats were excluded from foraging and lowest on branches without exclosures where both birds and bats were present. In the island plots, birds and bats had approximately equal impacts on insect populations, while in plantations bats appeared to have a slightly stronger effect on insects than did birds. In plantations, the levels of leaf damage were higher on branches where birds and bats were excluded than on branches where both had access. In island plots, no significant differences in leaf damage were found between exclosure treatments although potential patterns were in the same direction as in the plantations. Our results suggest that both birds and bats play important roles as top predators in restoration systems by reducing herbivorous insects and their damage to planted trees. Tropical restoration projects should include efforts to attract and provide suitable habitat for birds and bats, given their demonstrated ecological importance.

Collaboration between mental health and vocational rehabilitation programs for transition-age youth vocational outcomes.

Transition-age youth (TAY) with serious mental health conditions (SMHC) face many challenges as they establish adult employment. Mental health (MH) programs and vocational rehabilitation (VR) programs each provide key supports toward this goal, but collaboration is required. OBJECTIVE: The present study's objective was to assess the extent of collaboration between VR programs and MH programs that serve this age group and to identify interorganizational factors associated with collaboration levels. METHOD: Participants were 100 key informants from VR, and child mental health (CMH), transition-age youth MH (TAYMH), and adult mental health (AMH) programs in communities that received federal funding to improve services for TAY with or at risk of SMHC. Participants completed web surveys that queried four interorganizational factors and employed a modified social network analysis methodology to assess collaboration levels. RESULTS: The interorganizational factor, depth of knowledge, had a strong and consistent association with collaboration levels. There was little difference in MH-VR collaboration levels between MH programs serving different age groups. However, VR programs and CMH programs had both lower depth of knowledge of each other and lower collaboration levels, compared to TAY and AMH programs. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Collaboration between VR and MH programs is instrumental to making sure that TAY with SMHC receive appropriate career development and employment services. Increasing the depth of knowledge that programs have about each other may enhance collaboration and appears particularly needed between VR and CMH programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Method to assess the potential magnitude of terrestrial European avian population reductions from ingestion of lead ammunition.

Current estimates of terrestrial bird losses across Europe from ingestion of lead ammunition are based on uncertain or generic assumptions. A method is needed to develop defensible European-specific estimates compatible with available data that does not require long-term field studies. We propose a 2-step method using carcass data and population models. The method estimates percentage of deaths diagnosed as directly caused by lead poisoning as a lower bound and, as an upper bound, the percentage of possible deaths from sublethal lead poisoning that weakens birds, making them susceptible to death by other causes. We use these estimates to modify known population-level annual mortality. Our method also allows for potential reductions in reproduction from lead shot ingestion because reductions in survival and reproduction are entered into population models of species with life histories representative of the most groups of susceptible species. The models estimate the sustainability and potential population decreases from lead poisoning in Europe. Using the best available data, we demonstrate the method on two taxonomic groups of birds: gallinaceous birds and diurnal raptors. The direction of the population trends affects the estimate, and we incorporated such trends into the method. Our midpoint estimates of the reduction in population size of the European gallinaceous bird (< 2%) group and raptor group (2.9-7.7%) depend on the species life history, maximum growth rate, population trend, and if reproduction is assumed to be reduced. Our estimates can be refined as more information becomes available in countries with data gaps. We advocate use of this method to improve upon or supplement approaches currently being used. As we demonstrate, the method also can be applied to individual species of concern if enough data across countries are available.

Peer Academic Supports for Success (PASS) for College Students with Mental Illness: Open Trial.

Increasing numbers of college students have serious mental health conditions, but their dropout rates are high and debt accrual is common. A well-specified intervention that colleges can directly offer their undergraduates with serious mental health conditions that sustains their academic persistence is greatly needed. The Peer Academic Supports for Success (PASS) coaching model was developed to address this need. This study's goal was to conduct an open trial of the initial PASS model to test the feasibility of the model and research methods in preparation for more rigorous testing. Ten college juniors and seniors, with and without lived mental health experience, were hired, trained, and supervised to be PASS peer coaches. Twelve undergraduate students with academically impairing mental health conditions served as study participants and received PASS. Student data were collected at baseline and two semesters post baseline. Intervention feasibility data were assessed through coach report. Results indicate PASS can be delivered with fidelity by peer coaches, can attract and retain students, and is safe. Results also suggest that PASS has significant effects on most of the targeted proximal outcomes. The PASS findings are promising as a college-based intervention to support young adult students with mental health conditions.

Surgical and medical management in the treatment of proximal tibial metaphyseal fracture in immature dogs.

The purpose of this study was to report approaches to surgical and medical management of proximal tibial metaphyseal fractures (PTMF) and short-term case outcome. Medical records of immature dogs with PTMF were reviewed and data were collected including history, signalment and side affected. Data pertaining to surgical and medical management including radiographic evaluation and short-term complications were recorded. Forty-five dogs with a total of 47 PTMF identified and treated between 2007-2019 were included in this study. Six cases were managed with external coaptation alone. Forty-one cases were treated surgically with constructs including K-wires in different configurations, bone plate and screws, and external skeletal fixation. Of the cases managed conservatively, 4 developed complications, including bandage sores, diffuse osteopenia of the tarsus/metatarsus, and angular limb deformities. Surgical complications including pin migration necessitating removal, osteopenia, and screw placement in the proximal tibial growth plate or into the stifle joint were found in 16 cases. PTMF treated with surgery had a subjectively more predictable outcome compared to those treated with external coaptation alone. Conservative management may result in complications including development of excessive tibial plateau angle (TPA) as well as distal tibial valgus.

The effects of sex and neuter status on trauma survival in dogs: A Veterinary Committee on Trauma registry study.

OBJECTIVE: To determine the effect of sex and neuter status on trauma survival in dogs. DESIGN: Multi-institutional prospective case series, September 2013 to March 2019, retrospectively analyzed. SETTING: Level I and II Veterinary Trauma Centers. ANIMALS: Consecutive sample of 2649 dogs in the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma patient registry meeting inclusion criteria. For inclusion, dogs had to have complete data entries, be postpubertal (≥7 months age in females and ≥10 months age in males), and have sustained moderate to severe trauma (animal trauma triage [ATT] score ≥5/18). Dogs that were dead upon arrival, euthanized for financial or unknown reasons alone, or that were presented by a Good Samaritan but subsequently humanely euthanized were excluded. MEASUREMENTS AND MAIN RESULTS: Data collected included age, sex, neuter status (intact, neutered), trauma type (blunt, penetrating, both), outcome (survived to hospital discharge, died, euthanized), and reason for euthanasia (grave prognosis, financial reasons, or both). Of 2649 eligible dogs, 56% survived to hospital discharge (n = 1469). Neutered females had a significantly higher survival rate (58.3% vs 51.3%; P = 0.03) compared to intact females, and neutered males had a significantly higher survival rate (56.6% vs 50.7%; P = 0.04) compared to intact males. There was no significant difference in survival between intact females and intact males (P = 0.87) or between neutered females and neutered males (P = 0.46). Mean cumulative ATT score was higher in intact groups and was found to be a significant predictor of survival (P < 0.01). Based on logistic models, overall odds of survival were 20.7% greater in neutered dogs. CONCLUSIONS: Gonadectomy is associated with lower ATT scores and improved survival after moderate to severe trauma in both female and male dogs.

The Candida albicans Kar2 protein is essential and functions during the translocation of proteins into the endoplasmic reticulum.

Since the secretory pathway is essential for Candida albicans to transition from a commensal organism to a pathogen, an understanding of how this pathway functions may be beneficial for identifying novel drug targets to prevent candidiasis. We have cloned the C. albicans KAR2 gene, which performs many roles during the translocation of proteins into the endoplasmic reticulum (ER) during the first committed step of the secretory pathway in many eukaryotes. Our results show that C. albicans KAR2 is essential, and that the encoded protein rescues a temperature-sensitive growth defect found in a Saccharomyces cerevisiae strain harboring a mutant form of the Kar2 protein. Additionally, S. cerevisiae containing CaKAR2 as the sole copy of this essential gene are viable, and ER microsomes prepared from this strain exhibit wild-type levels of post-translational translocation during in vitro translocation assays. Finally, ER microsomes isolated from a C. albicans strain expressing reduced amounts of KAR2 mRNA are defective for in vitro translocation of a secreted substrate protein, establishing a new method to study ER translocation in this organism. Together, these results suggest that C. albicans Kar2p functions during the translocation of proteins into the ER during the first step of the secretory pathway.

Reported health and social consequences of the COVID-19 pandemic on vulnerable populations and implemented solutions in six West African countries: A media content analysis.

Coronavirus has spread worldwide with over 140 million cases and resulting in more than 3 million deaths between November 2019 to April 2021, threatening the socio-economic and psychosocial stability of many families and communities. There has been limited research to understand the consequences of COVID-19 on vulnerable populations in West Africa, and whether such consequences differ by countries' previous experience with Ebola. Using a media analysis of leading online news sources, this study identified the populations particularly vulnerable to the threats of the COVID-19 pandemic, described the consequences of COVID-19 experienced by these populations, and reported on the solutions to address them. All articles from the selected news sources published between January 1 and June 30, 2020 on 6 West African countries were imported into Dedoose. A total of 4,388 news articles were coded for excerpts on vulnerable populations, only 285 excerpts of which mentioned the existing effects of COVID-19 on vulnerable populations or implemented solutions. News articles from countries with past experience with Ebola were more likely to mention the pandemic's effects on vulnerable populations, especially on incarcerated people. Vulnerable groups were reported to have experienced a range of effects including economic disruptions, heightened domestic and sexual abuse, arbitrary arrests, health care inaccessibility, and educational challenges throughout the pandemic. With implications for the achievement of the Sustainable Development Goals (SDG) for 2030 in West Africa, these countries should consider and focus more strategic efforts on vulnerable populations to overcome their fight against the COVID-19 pandemic and to achieve the SDG for 2030.

Evaluation of matrix metalloproteinases and tissue inhibitors of metalloproteinases in aqueous humor of dogs with versus without naturally occurring primary angle-closure glaucoma.

OBJECTIVE: To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG). SAMPLE: Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs. PROCEDURES: A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared. RESULTS: Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes. CLINICAL RELEVANCE: MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.

COVID-19 Pandemic and Pediatric Type 1 Diabetes: No Significant Change in Glycemic Control During The Pandemic Lockdown of 2020.

Importance: There is no consensus on the impact of the 2020 COVID-19 pandemic lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) in the US. Aim: To determine the impact of the pandemic lockdown of March 15th through July 6th, 2020 on glycemic control after controlling for confounders. Subjects and Methods: An observational study of 110 subjects of mean age 14.8 ± 4.9 years(y), [male 15.4 ± 4.0y, (n=57); female 14.1 ± 3.8y, (n=53), p=0.07] with T1D of 6.31 ± 4.3y (95% CI 1.0-19.7y). Data were collected at 1-4 months before the lockdown and 1-4 months following the lifting of the lockdown at their first post-lockdown clinic visit. Results: There was no significant change in A1c between the pre- and post-pandemic lockdown periods, 0.18 ± 1.2%, (95% CI -0.05 to 0.41), p=0.13. There were equally no significant differences in A1c between the male and female subjects, -0.16 ± 1.2 vs -0.19 ± 1.2%, p=0.8; insulin pump users and non-pump users, -0.25 ± 1.0 vs -0.12 ± 1.4%, p=0.5; and pubertal vs prepubertal subjects, 0.18 ± 1.3 vs -0.11 ± 0.3%, p=0.6. The significant predictors of decrease in A1c were pre-lockdown A1c (p<0.0001) and the use of CGM (p=0.019). The CGM users had significant reductions in point-of-care A1c (0.4 ± 0.6%, p=0.0012), the CGM-estimated A1c (p=0.0076), mean glucose concentration (p=0.022), a significant increase in sensor usage (p=0.012), with no change in total daily dose of insulin (TDDI). The non-CGM users had significantly increased TDDI (p<0.0001) but no change in HbA1c, 0.06 ± 1.8%, p=0.86. Conclusions: There was no change in glycemic control during the pandemic lockdown of 2020 in US children.

Model and Data Concur and Explain the Coexistence of Two Very Distinct Animal Behavioral Types.

Behaviors may enhance fitness in some situations while being detrimental in others. Linked behaviors (behavioral syndromes) may be central to understanding the maintenance of behavioral variability in natural populations. The spillover hypothesis of premating sexual cannibalism by females explains genetically determined female aggression towards both prey and males: growth to a larger size translates into higher fecundity, but at the risk of insufficient sperm acquisition. Here, we use an individual-based model to determine the ecological scenarios under which this spillover strategy is more likely to evolve over a strategy in which females attack approaching males only once the female has previously secured sperm. We found that a classic spillover strategy could never prevail. However, a more realistic early-spillover strategy, in which females become adults earlier in addition to reaching a larger size, could be maintained in some ecological scenarios and even invade a population of females following the other strategy. We also found under some ecological scenarios that both behavioral types coexist through frequency-dependent selection. Additionally, using data from the spider Lycosa hispanica, we provide strong support for the prediction that the two strategies may coexist in the wild. Our results clarify how animal personalities evolve and are maintained in nature.